Chemotherapy + Immunotherapy for Breast Cancer

Overseen By Adrienne Gropper Waks, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Dana-Farber Cancer Institute

Must not be taking: CYP3A4 inhibitors, Immunosuppressants

Disqualifiers: Uncontrolled hypertension, Diabetes, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

Duration: 14-15 weeks

32 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does mention that you should avoid using potent CYP3A4 inhibitors like ketoconazole and erythromycin during the study. Participants on bisphosphonates can continue their therapy.

What data supports the effectiveness of the drug combination of nab-paclitaxel and pembrolizumab for breast cancer?

Nab-paclitaxel, a component of the treatment, has shown significant effectiveness in treating metastatic breast cancer, with rapid and dramatic tumor responses in patients with poor prognostic factors. Additionally, it is approved for use in metastatic breast cancer due to its superior therapeutic index compared to conventional paclitaxel. ^{1 2 3 4 5}

Is the combination of chemotherapy and immunotherapy safe for breast cancer treatment?

Nab-paclitaxel (Abraxane) has been studied for safety in various cancers, including breast cancer, and is generally considered safe, though it can cause side effects like any chemotherapy. It is a special form of paclitaxel that is designed to be easier on the body, and studies have shown it to be well-tolerated in patients with different types of cancer. ^{1 2 6 7 8}

What makes the drug combination of Nab-Paclitaxel and Pembrolizumab unique for breast cancer treatment?

This drug combination is unique because Nab-Paclitaxel is a novel formulation of paclitaxel that doesn't require toxic solvents, making it safer and potentially more effective by increasing drug concentration in tumors. Pembrolizumab, an immunotherapy, works by helping the immune system recognize and attack cancer cells, offering a dual approach by combining chemotherapy and immunotherapy. ^{1 3 5 9 10}

What is the purpose of this trial?

This research study is exploring chemotherapy in combination with immunotherapy (a therapy that uses the body's own immune system to control cancer) as a possible treatment for hormone receptor positive breast cancer. The interventions involved in this study are: * Pembrolizumab (MK-3475; Keytruda™) * Nab-Paclitaxel (Abraxane

Research Team

Adrienne Gropper Waks, MD

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

This trial is for adults with hormone receptor-positive, HER2-negative operable breast cancer larger than 2 cm without distant metastasis. They must not have had prior treatments for this cancer and agree to use contraception. Participants need normal organ/marrow function, no active autoimmune diseases or infections, and can't be on systemic steroids/immunosuppressants.

Inclusion Criteria

I am fully active and can carry on all pre-disease activities without restriction.

My breast cancer is hormone receptor-positive and HER2-negative.

My breast cancer is operable and my tumor is at least 2 cm big.

Exclusion Criteria

You have been diagnosed with Hepatitis B or Hepatitis C.

I have a history of lung inflammation not caused by an infection.

You are allergic to pembrolizumab or any of the ingredients in it.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Nab-Paclitaxel and Pembrolizumab. Nab-Paclitaxel is administered weekly and Pembrolizumab every 3 weeks for a total of 14-15 weeks.

14-15 weeks

Weekly visits for Nab-Paclitaxel, every 3 weeks for Pembrolizumab

Follow-up

Participants are monitored for safety and effectiveness after treatment, including changes in PD-L1 expression and overall response rate.

2 years

Long-term Follow-up

Participants are monitored for disease-free survival and other long-term outcomes.

3 years from randomization

Treatment Details

Interventions

• Biopsy
• Nab-Paclitaxel
• Pembrolizumab

Trial Overview The study tests chemotherapy (Nab-Paclitaxel) combined with immunotherapy (Pembrolizumab) in treating hormone receptor-positive breast cancer. It includes preoperative treatment and requires participants to undergo three research biopsies during the therapy.

Participant Groups

Group I: Pembrolizumab Experimental Treatment 3 Interventions

* 2 weeks Pembrolizumab Run in * Biopsy will be performed * Post mono therapy Nab-Paclitaxel administered weekly * Post mono therapy Pembrolizumab administered every 3 weeks * Agents administered for a total of 14 weeks

Group II: Nab-Paclitaxel Experimental Treatment 3 Interventions

* 2 weeks Nab-Paclitaxel Run in * Biopsy will be performed * Post mono therapy Nab-Paclitaxel administered weekly * Post mono therapy Pembrolizumab administered every 3 weeks * Agents administered for a total of 15 weeks

Nab-Paclitaxel is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Abraxane for:

• Breast cancer
• Pancreatic cancer
• Non-small cell lung cancer

Approved in European Union as Abraxane for:

• Breast cancer
• Pancreatic cancer

Approved in Canada as Abraxane for:

• Breast cancer
• Pancreatic cancer
• Non-small cell lung cancer
• Ovarian cancer

Who Is Running the Clinical Trial?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

Adrienne G. Waks

Lead Sponsor

Trials

4

Recruited

240+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Findings from Research

Nab-paclitaxel was well tolerated in pediatric solid tumor models, with a maximum weight loss of about 10% that returned to baseline after treatment, indicating a favorable safety profile.

The treatment showed significant efficacy, improving event-free survival in 19 out of 20 solid tumor xenograft models, particularly demonstrating high activity against Ewing sarcoma and rhabdomyosarcoma, making it a promising candidate for further pediatric evaluation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Initial testing (stage 1) of the tubulin binding agent nanoparticle albumin-bound (nab) paclitaxel (Abraxane(®)) by the Pediatric Preclinical Testing Program (PPTP). Houghton, PJ., Kurmasheva, RT., Kolb, EA., et al.[2022]

In a study involving 74 patients with metastatic melanoma, nab-Paclitaxel showed a response rate of 21.6% in chemotherapy-naive patients and 2.7% in previously treated patients, indicating better efficacy in those who had not undergone prior treatment.

The treatment was well tolerated, with 78% of previously treated patients and 49% of chemotherapy-naive patients able to complete therapy without dose reductions, suggesting a favorable safety profile compared to standard therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 2 clinical trial of nab-paclitaxel in previously treated and chemotherapy-naive patients with metastatic melanoma. Hersh, EM., O'Day, SJ., Ribas, A., et al.[2020]

In a study of 81 women with early-stage estrogen receptor-positive breast cancer, nab-Paclitaxel showed significant antitumor activity with a good response rate (RCB 0+I) of 24.7%, indicating its effectiveness as a neoadjuvant treatment despite a higher than expected poor response rate (RCB III) of 28.4%.

The treatment was associated with low rates of severe toxicity, with neutropenia being the most common side effect, and an exploratory analysis suggested that overexpression of the SPARC protein in tumors may predict a complete response, highlighting the need for further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant Therapy with Weekly Nanoparticle Albumin-Bound Paclitaxel for Luminal Early Breast Cancer Patients: Results from the NABRAX Study (GEICAM/2011-02), a Multicenter, Non-Randomized, Phase II Trial, with a Companion Biomarker Analysis. Martín, M., Chacón, JI., Antón, A., et al.[2021]

Nab-paclitaxel (Abraxane) is an effective treatment for metastatic breast cancer, showing a superior therapeutic index compared to conventional paclitaxel in a Phase III study with a standard dose of 260 mg/m² every three weeks.

In patients with poor prognostic factors, nab-paclitaxel demonstrated rapid and significant tumor responses, indicating it may be particularly beneficial for those with more severe disease, and lower doses (100 and 150 mg/m² weekly) also showed promising efficacy, suggesting potential for dose tailoring in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluating the role of nab-paclitaxel (Abraxane) in women with aggressive metastatic breast cancer. Ciruelos, E., Jackisch, C.[2015]

In a study involving 17 patients with malignant solid tumors, nab-paclitaxel (Abraxane) showed a significantly higher exposure to unbound paclitaxel compared to solvent-based paclitaxel, which may enhance its effectiveness against tumors.

The pharmacokinetics of nab-paclitaxel remained consistent across treatment cycles, indicating stable drug behavior and suggesting improved tolerability and efficacy due to its unique formulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized crossover pharmacokinetic study of solvent-based paclitaxel and nab-paclitaxel. Gardner, ER., Dahut, WL., Scripture, CD., et al.[2022]

In a phase II study involving 43 patients with non-small-cell lung cancer, Abraxane (260 mg/m2) demonstrated a 16% overall response rate and a 49% disease control rate, indicating its efficacy as a first-line therapy.

Abraxane was well tolerated, with no severe hypersensitivity reactions reported and only 5% of patients discontinuing treatment due to mild toxicities, suggesting a favorable safety profile for this novel formulation of paclitaxel.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abraxane, a novel Cremophor-free, albumin-bound particle form of paclitaxel for the treatment of advanced non-small-cell lung cancer. Green, MR., Manikhas, GM., Orlov, S., et al.[2022]

In a study of women with metastatic breast cancer treated with nab-paclitaxel, 43% experienced a clinical benefit, with a median survival of 63.6 weeks, indicating its effectiveness as a treatment option.

Nab-paclitaxel was well tolerated, with no severe hypersensitivity reactions reported and mild sensory neuropathy being the most common side effect, suggesting a favorable safety profile compared to traditional chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Retrospective Study of Efficacy and Safety of Albumin-Bound Paclitaxel in Metastatic Breast Cancer. Singh, RK., Pankaj, S., Kumar, S., et al.[2022]

Nanoparticle albumin-bound paclitaxel (ABI-007, Abraxane) is a safer alternative to conventional paclitaxel for breast cancer treatment, as it eliminates the need for toxic solvents and premedication.

Recent trials indicate that ABI-007 is well tolerated and offers superior outcomes compared to standard paclitaxel, including higher response rates, longer time to tumor progression, and extended survival in patients with metastatic breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nanoparticle albumin-bound paclitaxel (ABI-007): a newer taxane alternative in breast cancer. Moreno-Aspitia, A., Perez, EA.[2023]

ABI-007, a solvent-free albumin-bound paclitaxel, showed significantly higher response rates (33% vs. 19%) and longer time to tumor progression (23.0 weeks vs. 16.9 weeks) compared to standard paclitaxel in a phase III study with 454 patients.

ABI-007 had a lower incidence of severe neutropenia (9% vs. 22%) and did not require premedication, indicating a better safety profile, although it was associated with a higher rate of manageable sensory neuropathy (10% vs. 2%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase III trial of nanoparticle albumin-bound paclitaxel compared with polyethylated castor oil-based paclitaxel in women with breast cancer. Gradishar, WJ., Tjulandin, S., Davidson, N., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

Initial testing (stage 1) of the tubulin binding agent nanoparticle albumin-bound (nab) paclitaxel (Abraxane(®)) by the Pediatric Preclinical Testing Program (PPTP). [2022]

2. United States pubmed.ncbi.nlm.nih.gov

A phase 2 clinical trial of nab-paclitaxel in previously treated and chemotherapy-naive patients with metastatic melanoma. [2020]

3. England pubmed.ncbi.nlm.nih.gov

Neoadjuvant Therapy with Weekly Nanoparticle Albumin-Bound Paclitaxel for Luminal Early Breast Cancer Patients: Results from the NABRAX Study (GEICAM/2011-02), a Multicenter, Non-Randomized, Phase II Trial, with a Companion Biomarker Analysis. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Evaluating the role of nab-paclitaxel (Abraxane) in women with aggressive metastatic breast cancer. [2015]

5. Japan pubmed.ncbi.nlm.nih.gov

Neoadjuvant chemotherapy using nanoparticle albumin-bound paclitaxel plus trastuzumab and pertuzumab followed by epirubicin and cyclophosphamide for operable HER2-positive primary breast cancer: a multicenter phase II clinical trial (PerSeUS-BC04). [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Randomized crossover pharmacokinetic study of solvent-based paclitaxel and nab-paclitaxel. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Abraxane, a novel Cremophor-free, albumin-bound particle form of paclitaxel for the treatment of advanced non-small-cell lung cancer. [2022]

8. Canada pubmed.ncbi.nlm.nih.gov

A Retrospective Study of Efficacy and Safety of Albumin-Bound Paclitaxel in Metastatic Breast Cancer. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Nanoparticle albumin-bound paclitaxel (ABI-007): a newer taxane alternative in breast cancer. [2023]

10. United States pubmed.ncbi.nlm.nih.gov

Phase III trial of nanoparticle albumin-bound paclitaxel compared with polyethylated castor oil-based paclitaxel in women with breast cancer. [2023]